Synthesis of Triazenoazaindoles: a New Class of Triazenes with Antitumor Activity

Despite improvements in the treatment and prevention of cancer, the number of new diagnoses continues to rise; this has fuelled substantial interest in the development of new and effective chemotherapeutic agents. Compounds of the triazene class, such as dacarbazine, have been used in the clinical management of many cancer types including brain, leukemia, and melanoma. A new compound class bearing a triazenoazaindole scaffold was synthesized with the aim of identifying new antiproliferative agents. Compounds 5a-g and 6a-c were screened against a panel of human tumor cell lines, and two of them, 5e and 5f, showed cytotoxicity (GI50 range: 2.2-8.2\u3bcM) in all cell lines. These two compounds even maintained their cytotoxicity in some multidrug-resistant cell lines. Flow cytometry analysis demonstrated their ability to induce cell death by apoptosis with involvement of lysosomes. A kinder, gentler chemo: Triazenes have been used in the clinical management of many tumor types. Given the side effects of current chemotherapies and the emergence of drug-resistant tumors, there is great interest in molecules that bind and interact with DNA. Herein we describe triazenoazaindoles that show micromolar antiproliferative activity by inducing lysosome-mediated apoptosis